1iyj
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STRUCTURE OF A BRCA2-DSS1 COMPLEX
OverviewOverview
Mutations in the BRCA2 (breast cancer susceptibility gene 2) tumor, suppressor lead to chromosomal instability due to defects in the repair of, double-strand DNA breaks (DSBs) by homologous recombination, but BRCA2's, role in this process has been unclear. Here, we present the 3.1 angstrom, crystal structure of a approximately 90-kilodalton BRCA2 domain bound to, DSS1, which reveals three oligonucleotide-binding (OB) folds and a, helix-turn-helix (HTH) motif. We also (i) demonstrate that this BRCA2, domain binds single-stranded DNA, (ii) present its 3.5 angstrom structure, bound to oligo(dT)9, (iii) provide data that implicate the HTH motif in, dsDNA binding, and (iv) show that BRCA2 stimulates RAD51-mediated, recombination in vitro. These findings establish that BRCA2 functions, directly in homologous recombination and provide a structural and, biochemical basis for understanding the loss of recombination-mediated DSB, repair in BRCA2-associated cancers.
DiseaseDisease
Known disease associated with this structure: Split hand/foot malformation, type 1 OMIM:[183600]
About this StructureAbout this Structure
1IYJ is a Protein complex structure of sequences from Homo sapiens and Rattus norvegicus. Full crystallographic information is available from OCA.
ReferenceReference
BRCA2 function in DNA binding and recombination from a BRCA2-DSS1-ssDNA structure., Yang H, Jeffrey PD, Miller J, Kinnucan E, Sun Y, Thoma NH, Zheng N, Chen PL, Lee WH, Pavletich NP, Science. 2002 Sep 13;297(5588):1837-48. PMID:12228710
Page seeded by OCA on Mon Nov 12 17:35:59 2007